title: Silencing of c-Fos expression by microRNA-155 is critical for dendritic cell maturation and function.
abstract: MicroRNAs (miRNAs) are small, noncoding RNAs that regulate target mRNAs by binding to their 3' untranslated regions. There is growing evidence that microRNA-155 (miR155) modulates gene expression in various cell types of the immune system and is a prominent player in the regulation of innate and adaptive immune responses. To define the role of miR155 in dendritic cells (DCs) we performed a detailed analysis of its expression and function in human and mouse DCs. A strong increase in miR155 expression was found to be a general and evolutionarily conserved feature associated with the activation of DCs by diverse maturation stimuli in all DC subtypes tested. Analysis of miR155-deficient DCs demonstrated that miR155 induction is required for efficient DC maturation and is critical for the ability of DCs to promote antigen-specific T-cell activation. Expression-profiling studies performed with miR155(-/-) DCs and DCs overexpressing miR155, combined with functional assays, revealed that the mRNA encoding the transcription factor c-Fos is a direct target of miR155. Finally, all of the phenotypic and functional defects exhibited by miR155(-/-) DCs could be reproduced by deregulated c-Fos expression. These results indicate that silencing of c-Fos expression by miR155 is a conserved process that is required for DC maturation and function.
authors.affiliation: Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dunand-Sauthier
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Santiago-Raber
authors.forename: Leonardo
authors.initials: L
authors.lastname: Capponi
authors.forename: Charles E
authors.initials: CE
authors.lastname: Vejnar
authors.forename: Olivier
authors.initials: O
authors.lastname: Schaad
authors.forename: Magali
authors.initials: M
authors.lastname: Irla
authors.forename: Queralt
authors.initials: Q
authors.lastname: Seguín-Estévez
authors.forename: Patrick
authors.initials: P
authors.lastname: Descombes
authors.forename: Evgeny M
authors.initials: EM
authors.lastname: Zdobnov
authors.forename: Hans
authors.initials: H
authors.lastname: Acha-Orbea
authors.forename: Walter
authors.initials: W
authors.lastname: Reith
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology*; D019143:Evolution, Molecular; D020868:Gene Silencing / Q000276:immunology*; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000166:cytology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger